Volume: 05

Drug Information Centre (DIC) Indian Pharmaceutical Association, Bengal Branch Tele fax: 033 24612776, E-mail: ipabengal.dic@gmail.com Web Site: http://www.ipabengal.org Contact: 09830136291

Drug Information Bulletin (Electronic)

th

Year

Number: 14

16th July 2011

Content National Essential Medicines List-2011 available at CDSCO website New Drug: Saxagliptin Risk of oral clefts in children born to mothers taking Topiramate Linagliptin approved for type 2 diabetes From aspirin to anaesthesia, drugs to be tracked Forthcoming Events Readers Column

National Essential Medicines List2011 available at CDSCO website The first Essential Drug List was published in the year of 1996, which was subsequently revised in the year of 2003 having 354 medicines. The 2011 edition of NEML contain 348 medicines out of which 181 has been earmarked for Primary, Secondary & Tertiary health care set up, 106 for the secondary and Tertiary and 61 for Tertiary care. Overall 47 medicines have been deleted from the 2003 edition and 43 new medicines have been included in the 2011 list. It may be noted that though the first edition has been published almost 14 years back no serious efforts were found for its implementation. Hope serious initiative will be taken to implement it in the health care facilities in India. For details: www.cdsco.nic.in New Drug: Saxagliptin

Onglyza (Bristol-Myers Squibb) 5 mg tablets Approved indication: type 2 diabetes Australian 10.1.3 Medicines Handbook section

Incretins help to lower blood glucose after a meal. This effect can be prolonged by inhibiting their metabolism. Sitagliptin and saxagliptin are drugs which do this by inhibiting the enzyme dipeptidyl peptidase 4 (DPP4) (see 'Incretin mimetics and enhancers' Aust Prescr 2008;31:102-8). Saxagliptin is taken once a day. After absorption, the drug suppresses DPP4 activity for 24 hours. Saxagliptin is metabolised by cytochrome P450 3A4 to a less potent active metabolite. The pharmacokinetics of saxagliptin can therefore be affected by other drugs which

act on P450 3A4. For example, inhibition by ketoconazole increases the concentration of saxagliptin and decreases the concentration of its active metabolite. Saxagliptin has a half-life of 2.5 hours and its main metabolite has a half-life of 3.1 hours. The drug and its metabolites are mainly excreted in the urine. It should not be used in patients with moderate or severe renal impairment. Saxagliptin has been studied as an add-on treatment for patients with type 2 diabetes that had not been controlled by a single drug. It was added to metformin in a placebo-controlled study of 743 patients. After 24 weeks of treatment, the 191 patients who took metformin with saxagliptin 5 mg had a reduction of 0.69% in their concentrations of glycated haemoglobin (HbA1c). There was a rise of 0.13% in the patients who added a placebo to metformin. Saxagliptin also significantly reduced fasting blood glucose.1 The relative benefits of increasing the dose of a sulfonylurea or adding saxagliptin were assessed in a study of 768 patients. All the patients were given glibenclamide 7.5 mg daily for four weeks. Patients whose diabetes was not controlled were then randomised to increase the dose to 10 mg daily or add saxagliptin 2.5 or 5 mg. After 24 weeks the mean HbA1c concentration had increased by 0.08% in the glibenclamide group, but decreased by 0.54% in patients who added saxagliptin 2.5 mg and by 0.64% in those who added 5 mg. The combination of treatments had a statistically significantly greater effect on fasting blood glucose than increasing the dose of glibenclamide.2 The mean reduction from baseline was 0.4 mmol/L with compared with an increase of 0.04 mmol/L with glibenclamide.

2 Saxagliptin has also been added to the treatment of patients whose diabetes has not been controlled by a thiazolidinedione. In this study, 565 patients taking pioglitazone or rosiglitazone were randomised to add saxagliptin 2.5 mg, 5 mg or a placebo. After 24 weeks the HbA1c concentration had fallen by 0.66% with 2.5 mg, 0.94% with 5 mg and 0.3% with placebo. The reductions in fasting blood glucose were also significantly greater with saxagliptin.3 One study used saxagliptin and metformin in 1306 patients who were starting treatment for the first time. After 24 weeks the combination reduced the concentrations of HbA1c and fasting blood glucose more than either drug alone. Metformin with saxagliptin 5 mg reduced HbA1c by 2.5% compared to 2.0% with metformin and 1.7% with saxagliptin 10 mg alone.4 During the trials 3.3% of the patients discontinued saxagliptin 5 mg because of adverse effects compared with 1.8% of the placebo groups. Reasons for stopping treatment included lymphopenia, rashes and increased creatinine concentrations. Hypoglycaemia was reported by 5.2% of patients when saxagliptin 5 mg was added to metformin,1 14.6% when added to glibenclamide2 and 2.7% when added to a thiazolidinedione.3 In the thiazolidinedione study 8.1% of the patients developed peripheral oedema when saxagliptin 5 mg was added to their treatment.3 Saxagliptin's main role is likely to be as an add-on therapy. Its modest efficacy will not bring every patient's diabetes under control. The proportion of patients achieving HbA1c concentrations under 7% after adding saxagliptin 5 mg was 43.5% with metformin,1 22.8% with glibenclamide2 and 41.8% with a thiazolidinedione.3 Continuing diet and

3 exercise is therefore important. Although saxagliptin has been approved for use with metformin as an initial drug treatment, it is not usual practice to begin treatment with a combination of drugs. As diabetes is a chronic disease, it will be years before the clinical effectiveness and safety of saxagliptin can be confirmed. References* 1. DeFronzo RA, Hissa MN, Garber AJ, Luiz Gross J, Yuyan Duan R, Ravichandran S, et al. The efficacy and safety of saxagliptin when added to metformin therapy in patients with inadequately controlled type 2 diabetes with metformin saxagliptin 2.5 mg and 0.5 mmol/L with saxagliptin 5 mg, alone. Diabetes Care 2009;32:164955. 2. Chacra AR, Tan GH, Apanovitch A, Ravichandran S, List J, Chen R, et al. Saxagliptin added to a submaximal dose of sulphonylurea improves glycaemic control compared with uptitration of sulphonylurea in patients with type 2 diabetes: a randomised controlled trial. Int J Clin Pract 2009;63:1395406. 3. Hollander P, Li J, Allen E, Chen R; CV181-013 Investigators. Saxagliptin added to a thiazolidinedione improves glycemic control in patients with type 2 diabetes and inadequate control on thiazolidinedione alone. J Clin Endocrinol Metab 2009;94:4810-9. 4. Jadzinsky M, Pftzner A, PazPacheco E, Xu Z, Allen E, Chen R, et al. Saxagliptin given in combination with metformin as initial therapy improves glycaemic control in patients with type 2 diabetes compared with either monotherapy: a randomized controlled trial. Diabetes Obes Metab 2009;11:61122.
Source: Aust Prescr 2011;34:89-91

Risk of oral clefts in children born to mothers taking Topiramate The Food and Drug Administration (FDA) is informing the public of new data that show that there is an increased risk for the development of oral clefts in infants of women treated with topiramate (Topamax and generic products) during pregnancy. Topiramate is an anticonvulsant used to treat epilepsy. It is approved for use to prevent migraine headaches. Topiramate is being placed in Pregnancy Category D indicating positive evidence of human fetal risk but with potential benefits that may be acceptable in certain situations despite its risks. Reference: FDA Drug Safety Communication, 4 March 2011 at http://www.fda.gov/Drugs/Drug Safety WHO training co Linagliptin approved for type 2 diabetes The Food and Drug Administration (FDA) has approved linagliptin (Tradjenta) tablets for use with diet and exercise, to improve blood glucose control in adults with Type 2 diabetes which is the most common form of the disease, affecting between 90 and 95% of the 24 million diabetics in the United States. Linagliptin was demonstrated to be safe and effective in eight double-blind, placebocontrolled clinical studies involving about 3800 patients with Type 2 diabetes. Linagliptin has been studied as a standalone therapy and in combination with other type 2 diabetes therapies including metformin, glimepiride, and pioglitazone.

4 Linagliptin has not been studied in combination with insulin, and should not be used to treat people with type 1 diabetes or in those who have diabetic ketoacidosis. Reference: FDA News Release, 2 May 2011 at http://www.fda.gov From aspirin to anaesthesia, drugs to be tracked The Union health ministry has constituted a task force under the chairmanship of H G Koshia, Commissioner, Food and Drugs Control Administration (FDCA), Gujarat, for developing software that could be used to track drugs - right from manufacturers to retailers - to check the menace of counterfeit drugs in the country. A step in this direction came from the Allahabad High Court in the criminal writ petition (no 16212/2008 Brahmaji vs State of UP and others) for developing a drug tracking system. Addressing the press after the third meeting with various stakeholders from the south, M Mitra, deputy drugs controller of India, said: "This task force was set up by the ministry to collect information on ways to implement the track and trace system in the country, for which there has been a mixed response from the industry."The task force comprises nine members from different ministries and from the drug controller offices, including Dr B Jagashetty, Drugs Controller, Karnataka, M Mitra, Deputy Drugs Controller, India, Vishawajit Ringe, Senior Technical Director, National Informatics Centre, representatives from department of consumer affairs and legal affairs, department of commerce, the under secretary of drugs quality control, ministry of health and family welfare, Rishikant Singh (legal), CDSCO, and E Reddy, assistant drugs controller. The task force will examine the feasibility of networking and tracking the drugs distribution system in the country. It will indicate the requirements for the software for drug tracking system to be developed by National Informatics Centre (NIC). It aims to examine different IT tools and methodologies and select the most suitable for implementation in the country. It will also suggest if bar coding and Unique identification number (UID) can in any way help in the networking of the drugs distribution with respect to manufacturing, import and export. The task force will also examine and suggest the requirements for different stake holders like manufacturers, distributors and retailers. The team will recommend amendments in the drugs and cosmetics rules with respect to drug distribution system and tracking.
Source: Express News Service, The New Indian Express

Forthcoming Event:

Readers Column: Dear Team, I must congratulate to you all for coming out with a good quality & highly informative Information bulletin periodically. I thank you to give me an opportunity to get myself enriched & exposed to such professional knowledge. My all good wishes are with you! Best Regards Shantanu Shome Dr. Reddy's Laboratories Limited Hyderabad